The mission of our laboratory is to elucidate the biology and evolution of human adenoviruses.
Virus induced signal transduction – Human adenoviruses are the etiologic agents of epidemic keratoconjunctivitis, a severe and highly transmissible infection of the eye. We have shown the primacy of Src, MAPK, and PI3K signaling in corneal infection by adenoviruses, and believe cell signaling represents fertile ground for development of novel therapeutics. We use primary cell culture, complex tissue culture reconstructions of the cornea, and transgenic and knockout mice to study the role of individual signaling molecules in adenovirus pathogenesis.
Innate immune responses to virus infection – We developed a mouse model of adenovirus keratitis, and used it to show that viral capsid was the major molecular pattern for innate immune responses in the cornea. Currently, we are investigating the specific roles of unique cell types present in the cornea in the early innate immune responses to viral infection. We want to elucidate the unique interactions between specific molecular patterns expressed by the adenovirus and individual corneal stromal and bone marrow derived cell phenotypes.
Adenovirus genomics and evolution – Concurrent with our interest in molecular patterns and innate immunity, we have turned our attention more closely to the adenovirus pathogen as a physical entity, and have completed whole genome sequencing of all the remaining unsequenced human adenoviral prototypes (no. = 20). This led to our confirmation of homologous recombination as a major mechanism for evolution of the virus. Our current focus is to understand the molecular basis for homologous recombination between human adenoviruses.